Production of prostaglandin D2 (PGD2) was investigated in cultured endothelial cells derived from capillaries and microvessels (small and large) of human brain using radioimmunoassays, Peptides, catecholamines, thrombin, protein kinase C-activating phorbol ester and calcium ionophore greatly stimulated the secretion of endothelial PGD2. Both vasoconstricting peptides, angiotensin II and arginine-vasopressin-inducible secretion of PGD2 was almost completely abolished by their respective specific receptor antagonists [Sarl, Ala8]-Ang 11 and [1-6(beta-mercapto-beta, beta-cyclopentamethylene propionic acid) 2-0-methyltyrosine. Thus, augmented production of PGD2 by angiotensin II and argininevasopressin is a receptor-mediated event. it also indicates that the EC have specific angiotensin II and arginine-vasopressin (V1) receptors. This study represents the first demonstration of vasoactive peptides modulating PGD2 production in capillary and microvascular endothelium of human brain.